Changing the surface antigenicity thereof by drifts, influenza viruses cause epidemics every year. Additionally, in a cycle of about 10 years to 40 years, new types of the viruses with antigenicity profiles totally different from those thereof have emerged as a result of shifts, which have caused worldwide extensive epidemics (hereinafter referred to as “pandemics”) among the human beings, which lack immunity to the new types of the viruses.
Spanish flu, Hong Kong flu and other pandemics in the past are said to be likely to have been caused by avian influenza virus; an estimation is available that 5.00 million to 150.00 million people will possibly die of avian influenza in the future. Currently, infections with highly pathogenic avian influenza (H5N1), which produces high mortality rates, are reported around the world; effective countermeasures are urgently needed.
Generally, influenza viruses, including avian influenza virus, are likely to undergo mutations in the process of proliferation. Furthermore, if a virus that has infected to a human reasserts with human influenza virus in the body, a virus highly infectious among human beings possibly emerges while retaining the high pathogenicity. These frequent alterations of the viruses themselves are a reason for the repeated epidemics described above.
Point mutations (antigen drifts) occur in the genes that encode viral surface glycoproteins [hemagglutinin (HA) and neuraminidase (NA)], whereas antigen shifts produce novel strains with both genes altered immunologically.
Conventional vaccines induce the production of an antibody that binds specifically to a surface protein of influenza virus, and by means of the action of this antibody, deprive virus of the infectious potential. However, the surface proteins are likely to undergo mutations, as stated above, so that the antibodies induced by the above-described vaccines have not always been effective. At present, vaccines are reserved according to the type of virus expected to be prevalent, but the expectation is possibly a disappointment resulting in expanded damage.
Meanwhile, an internal protein of influenza virus is relatively highly conserved even in drift mutants and shift mutants; it is difficult to deactivate the protein by binding an antibody thereto from outside the virus, so that the internal protein has not been used proactively as a target for conventional vaccines.
Virus-infected cells expose on the surfaces thereof a major histocompatibility antigen complex (MHC) incorporating a portion of the amino acid sequence of a viral internal protein. If cytotoxic T lymphocytes capable of specifically killing virus-infected cells exhibiting these features could be prepared, it would be possible to effectively prevent the replication, and hence proliferation and spread of the virus, without being influenced by mutations.
JP-A-2008-37831 discloses a method of preparing a T cell activator capable of efficiently and specifically augmenting cytotoxic T lymphocytes (CD8+ T cells, cytotoxic lymphocytes: CTL) for killing pathogen-infected cells or cancer cells using an antigen-bound liposome, and useful in the prevention or treatment of infectious diseases and cancers. However, it has been totally unclear whether the method can be actually effective in preventing infections with avian influenza virus, and what kind of antigen can be used to prepare effective cytotoxic T lymphocytes.